The general goal of this research is to understand the mechanism by which enveloped viruses infect cells. Since this process is thought to involve fusion of the virus membrane with that of the cell, the focus is on molecular events that underly membrane fusion. A model virus membrane has been developed which is a lipid vesicle composed of phosphatidylcholine, lysophosphatidylcholine and stearylamine. These membranes have been shown to carry out all the membrane-associated actions of parainfluenza viruses. It appears that the essential feature of the fusion of these vesicles with cell membranes is that the bilayer structure normally assumed by phosphatidylcholine is perturbed by the presence of lysophosphatidylcholine. During the second year of this grant, attempts will be made with simpler model lipid systems to determine whether general perturbation of bilayer organization by other molecules, such as hydrophobic proteins, will also facilitate fusion. Another aspect of this research involves investigating the details of interaction of intact parainfluenza virus with a model membrane consisting only a lipid bilayer into which the virus receptor protein has been incorporated. We will determine whether the virus membrane is able to fuse with the model cell membrane and if so, determine what the consequences are for the permeability of the model cell membranes and whether the lipid composition of the latter are critical for fusion.